News

Designer Babies and Education: the Age of CRISPR

March 18, 2016

Prof. El Bejjani working in the lab with Joe Zhou '17 and Nick Elder '18

Genes are the basic functional unit of heredity. Human genes determine multitudes of personal characteristics such as eye color, height, hair color and nail growth, as well as bodily functions, such as digestion and the transport of oxygen in the blood.

Now, however, scientists have discovered a means to bypass the glacial pace of natural genetic mutation and alter the genes of organisms in a highly precise, instantaneous manner. Named CRISPR_Cas9, this "genome editing" technology promises to accelerate many areas of scientific discovery. For example, edited genes could eliminate some genetic diseases, speed up medical research and help increase food production for the world.

While the discovery is giving hope to and being met with excitement by many researchers, it is also fueling concerns about the ethical implications of using a powerful new biological capability.

There are no plans in Davidson's biology department to grow super-sized tomatoes or resurrect a wooly mammoth, but faculty members are proceeding to introduce CRISPR instruction into their curricula and labs so students can explore the tool and carefully consider the implications of its use.

Precision & Power

CRISPR is an acronym for "clustered regularly interspaced short palindromic repeats," which describes the genetic basis of the method. Cas9 is the name of a protein that makes it work.

Researchers have been genetically modifying organisms since the 1970s. CRISPR, which was first described as a gene editing tool in a June 2012 article in the journal Science, is much more precise than traditional genetic modifications. CRISPR is also easier and less expensive to employ.

It was deemed so significant an invention that its creators, Jennifer Doudna and Emmanuelle Charpentier, were awarded a $3 million Breakthrough Prize in Life Science for 2015, and were listed among the 100 most influential people in the world by Time magazine.

A recent article in the Journal of Young Investigators explained the procedure:

"The procedure involves the Cas9 enzyme, which cuts the DNA double helix. Then a guide-RNA directs Cas9 to specific sites in the genome. If a cut is made in a gene, DNA repair machinery in the cell silences the gene. The main advantage of this technology is that it can be guided to very specific genetic sequences and ignore other sequences that are not meant to be targeted.

"By introducing a new DNA fragment with the Cas9-gRNA complex, the DNA repair machinery repairs the DNA by incorporating the new DNA where the cut was made. This way a specific mutation can be introduced into a gene, or a mutated gene can be replaced with a healthy one, or an entirely new gene can even be introduced into the cell DNA. Essentially, CRISPR-Cas9 allows scientists to manipulate cell DNA in an infinite number of ways... By cutting out or modifying a gene of interest, scientists can directly study the function of both healthy and mutated forms of the gene."

Scientists around the globe are excitedly launching experiments to test the potential of this new technique. One report estimated that three new peer-reviewed publications per day mention CRISPR.

Call for 'a Pause'

Speaking about CRISPR in a TED Talk last November, co-inventor Jennifer Doudna acknowledged its positive promise for mankind. She expectantly said that within a decade CRISPR will be used to cure genetic diseases like sickle cell anemia, cystic fibrosis and hemophilia.

But she also called for a "global pause" in its development, because, she said, "Genome engineered humans are no longer science fiction."

Scientists gathered last December for the International Summit for Gene Editing to discuss technologies like CRISPR and the ethics of using them.

Participants ended up calling for a moratorium on making DNA changes that could be passed along to future generations of humans, but stopped short of calling for a ban.

Research that affects only individuals is continuing concurrently with discussions about the technology led by thought leaders from around the world.

CRISPR in Davidson

Assistant Professor of Biology Rachid El Bejjani taught the college's first "Genetic Editing" class last fall, and plans to offer it once per year. YangYu Zhou '17, a biology major and computer science minor from Shanghai, was in that class. He is now working with El Bejjani on an independent study basis to conduct CRISPR experiments that El Bejjani began as a postdoctoral researcher.

Zhou and El Bejjani are using CRISPR to manipulate the genes of a tiny C. elegans worm, and study the genetic mechanisms of its nerve regeneration. They selected this organism because the creature's entire genome has been mapped. Additionally, it reproduces within three or four days, can be genetically modified in-house at Davidson, and its transparency makes it easier to monitor during the experimentation process.

The project will determine if two sets of genes shown to be involved in neuronal regeneration are regulating each other. This genetic regulation was predicted using computer software, but cannot be examined directly without CRISPR technology.

The popular science literature and news articles often give the impression that editing the genome can happen at the flip of a switch. In reality, the design and application remain technically challenging and can sometimes have a very low rate of success. Zhou has been spending two or three hours per day, including weekends, to accomplish the experimental design and to create the pieces of RNA required to guide the enzyme to cut. These steps are necessary before the gene can actually be cut.

Zhou will remain in Davidson over the summer to continue the research. He hopes to generate a new strain of C elegans and measure its phenotypes in regeneration and other biological functions. If he can manipulate its genes so that the new worm has no vulva, the work will have been a success.

He will then use this newly edited worm to see if the genes that he studies regulate each other as he predicted with software.

"When we do that we'll have done CRISPR, and we'll open the door to a lot of future experiments," he said.

Despite the long hours and some missteps, Zhou is thrilled with the opportunity. "I'm a science geek," he said confidently. "I love the work because I believe this technology will be the mainstream soon, and I see its potential to do good things like curing diseases and eliminating malaria."

He also enjoys working elbow-to-elbow with similarly motivated peers and helpful faculty.

"Doctor El Bejjani is very helpful, and my friends in the lab are awesome," he said. "We always talk about our work and help each other out. I love those close relationships with professors and students at Davidson."

Considering the Future

As they proceed with the scientific instruction, Davidson's CRISPR researchers are also considering the ethics of using this powerful tool. Will genetics researchers develop designer babies -- genetically modified children designed to contain traits of intelligence, beauty and/or health? And what about the potential for increasing societal inequality, as rich people choose physical characteristics for their children while the poor can't afford to consider it?

A recent Washington Post writer postulated that the impact of CRISPR will be much larger than anticipated. It will widen the overall horizon of discovery, leading to advances we can't even imagine.

The author wrote, "CRISPR is dramatically accelerating biological discovery by 'democratizing' gene editing and making it accessible to a huge number of people. It's staggering to imagine all of the amazing, completely unanticipated things that democratized gene editing will enable us to discover. This opportunity to dive deep into biological systems that were previously impenetrable is the real power of CRISPR."

Wherever the evolving science leads, it's certain that Davidson will bring talented faculty members together with eager students to explore the issues, and contribute to the public discussion.